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Abstract
Binding of an antibody to a plasma metalloprotease ADAMTS13 is required for the development of immune thrombotic thrombocytopenic purpura (iTTP). Inhibition of ADAMTS13-mediated VWF cleavage by such antibodies clearly plays a role in the pathophysiology of the disease, although the mechanisms by which they inhibit ADAMTS13 enzymatic function are not fully understood. At least some immunoglobulin G-type antibodies appear to affect the conformational accessibility of the ADAMTS13 domains involved in substrate recognition and inhibitory antibody binding. We used single variable region chain fragments (scFvs) previously identified by phage display from patients with iTTP to study the mechanisms of action of inhibitory human monoclonal antibodies. Using full-length recombinant ADAMTS13, truncated ADAMTS13 variants, and native ADAMTS13 in normal human plasma, we found that all three inhibitory monoclonal antibodies affect the rate of enzyme turnover much more than von Willebrand factor (VWF). . Hydrogen-deuterium exchange and mass spectrometry (HX-MS) experiments with each of these inhibitory antibodies revealed that residues in the active site of the ADAMTS13 catalytic domain are differentially exposed to solvent in the presence and absence of monoclonal antibody binding. These results support the hypothesis that inhibition of ADAMTS13 in iTTP is not necessarily due to antibodies preventing direct binding of VWF, but rather is due to allosteric effects that prevent VWF cleavage, likely through conformation of the catalytic center in the protease domain of ADAMTS13 to affect it. Our results provide new insights into the mechanism of autoantibody-mediated inhibition of ADAMTS13 and the pathogenesis of iTTP.
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Research Article
FLT3-ITD allele ratio and NPM1 mutation do not affect outcomes in patients with acute myelogenous leukemia with FLT3-ITD after allogeneic hematopoietic stem cell transplantation: a retrospective propensity score matching study
Transplantation and Cell Therapy, 2023
The FLT3-ITD mutation consistently correlates with poor outcomes in patients with acute myelogenous leukemia (AML). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in curing blood disorders. It is still questionable whether allo-HSCT can eliminate the side effects of the FLT3-ITD mutation in patients with AML. Furthermore, studies have shown that FLT3-ITD allele ratio (AR) and NPM1 mutation appear to further influence the prognostic utility of FLT3-ITD in patients with FLT3-ITD mutant AML. The influence of NPM1 and AR mutation on FLT3-ITDTampaThe patients in our database remain unclear. Our aim was to compare survival outcomes after allo-HSCT in patients with FLT3-ITDTampaand those with wild-type FLT3-ITD and to further analyze the impact of NPM1 and AR on outcomes. A total of 118 FLT3 ITDsTampapatients and 497 FLT3-ITDweightPatients undergoing allo-HSCT received a propensity score match of 1:3 using nearest neighbor matching with a caliper of 0.2. The study cohort consisted of 430 patients with AML, including 116 with FLT3-ITDTampaa 314 with FLT3-ITDweight. Overall survival (OS) and leukemia-free survival (LFS) were similar in the FLT3-ITDTampapatients and the FLT3-ITDweightpatients (2 years OS, 78.5% vs. 82.6% [P=.374]; 2-year LFS, 75.1% vs. 80.8% [P=.215]). A cutoff value of 0.50 was used to define RA subgroups with low and high FLT3-ITD. There were no significant differences in the cumulative incidence of recurrence (CIR) or LFS between the low RA group and the high RA group (2-year CIR,P=.617; 2 years LFS,P=.563). CIR and LFS were also comparable when patients were grouped by the presence or absence of NPM1 and FLT3-ITD (2 years CIR,P=.356; 2 years LFS,P=.159). In addition, the CIR and LFS of the FLT3-ITDTampaum ITD FLT3weightPatients tended to differ after HSCT from a matched sibling donor (2-year CIR,P=.072; 2 years LFS,P=.084); However, these differences were seen in recipients of a haploidentical (haplo-) HSCT (2-year CIR,P=.59; 2 years LFS,P=.794). The presence of minimal pre-transplant residual disease and lack of an initial complete response were identified as risk factors for worse outcomes in a multivariate analysis, regardless of FLT3-ITD or NPM1 status. Our results suggest that allo-HSCT, particularly haplo-HSCT, can overcome the adverse effect of the FLT3-ITD mutation regardless of NPM1 or AR status. Allo-HSCT may be an ideal option for AML patients with FLT3-ITD.
Research Article
Influence of iron overload and iron chelation with deferasirox on outcomes in patients with severe aplastic anemia after allogeneic hematopoietic stem cell transplantation
Transplantation and Cell Therapy, 2023
Patients with severe aplastic anemia (SAA) require regular blood transfusions during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these transfusions can lead to an excess of iron in body tissues, which can have a negative impact on the success of the transplant. The aim of this study was to investigate the influence of pre-transplant (IO) iron overload on allo-HSCT outcome in patients with AWS. It also examined whether iron chelation (IC) therapy is necessary to improve transplant outcomes in patients with AWS, providing guidelines for determining when to chelate excess iron. The study consisted of 2 parts. In retrospective cohort 1, conducted from April 2012 to December 2018, patients with AWS who received their first allo-HSCT were divided into two groups based on pre-transplant serum ferritin (SF) level: the IO group (SF > 1000). ng/ml; n=17) and the non-IO group (SF ≤1000 ng/mL; n=48). Cohort 2, a prospective clinical study conducted from January 2019 to July 2020, included patients with AAS diagnosed with OI treated with intensive therapy with deferasirox at a dose of 10 to 30 mg/kg. Patients were divided into two groups based on their pre-transplant SF score: IC success (ICSuccess) group (SF ≤1000 ng/mL; n=18) e or erro IC (ICFail) group (SF >1000 ng/mL; n=28). In all participants, the correlation between pre-transplant SF levels and transplant outcome was examined. APA value <0.05 was considered statistically significant. There was no significant difference in engraftment rate between the three cell lines or in the incidence of acute graft-versus-host disease (aGVHD) grade II-IV over 100 days, grade III-IV aGVHD, or chronic GVHD over 3 days. years between the two groups and both cohorts. However, it is noteworthy that in cohort 1 both had a 1-year overall survival (OS) (41.2% vs. 83.3%;P< 0.001) and OS at 3 years (35.3% vs. 83.3%;P< 0.001) were significantly worse in the IO group. Additional 180-day transplant mortality (TRM) (47.1% vs. 14.6%;P=.005) by TRM de 1 ano (52,9% vs. 16,7%;P=.002) were significantly higher in the IO group. The OI group was significantly associated with worse 3-year OS in univariate and multivariate analyses. In the 1-year cohort 2 OS (88.9% vs. 42.9%;P= 0.003) and 3-year OS (83.3% vs. 42.9%;P=.007) were significantly better in the intensive care unitSuccessgroup, during TRM of 180 days (11.1% vs. 39.3%;P= 0,040) by TRM de 1 type (11,1% vs. 57,1%;P=.003) were significantly lower in the intensive care unitSuccessGroup. These differences were confirmed in univariate and multivariate analyses. This 2-cohort study shows that pre-HSCT IO has a negative impact on transplant outcomes in patients with AWS. Chelation of excess iron with SF <1000 ng/mL proved to be necessary and could potentially improve results.
(Video) ISTH Academy Presentation: Acquired Thrombotic Thrombocytopenic PurpuraResearch Article
How to treat newly diagnosed and refractory acute T-cell lymphoblastic lymphoma in children and young adults
blood, 2023
T-cell lymphoblastic lymphoma (T-LLy) and T-cell acute lymphoblastic leukemia (T-ALL) have traditionally been seen as a spectrum of the same disease. However, recent evidence showing different responses to chemotherapy suggests that T-LLy and T-ALL are distinct clinical and biological entities. Here we examine the differences between the two diseases and, through illustrative cases, provide important recommendations for the best management of newly diagnosed and relapsed/refractory patients with T-LLy. We discuss the results of recent clinical trials involving the use of delarabine and bortezomib, the choice of induction steroids, the role of cranial radiotherapy, and risk stratification markers to identify patients at increased risk of recurrence and to further refine current treatment strategies. . As the prognosis for relapsed or refractory T-LLy patients is poor, we review ongoing studies that integrate new therapies, including immunotherapy, into advanced and salvage therapies and the role of hematopoietic stem cell transplantation.
Research Article
Characterization of the bone marrow niche in patients with chronic myelogenous leukemia identifies CXCL14 as a new therapeutic option
blood, 2023
Although tyrosine kinase inhibitors are effective in treating chronic myelogenous leukemia (CML), they usually fail to destroy leukemia initiating stem cells (LSCs), leading to disease progression and relapse. There is evidence that the persistence of LSC may be due to niche protection in the bone marrow (BM). However, little is known about the underlying mechanisms. Here, we molecularly and functionally characterize the BM niches in CML patients at the time of diagnosis and reveal the altered niche composition and function in CML patients. A long-term culture starter cell (LTC-IC) trial showed that mesenchymal stem cells from CML patients showed an improved carrying capacity for normal and CML-BM CD34+CD38-cells. From a molecular point of view, the dysregulated expression of cytokines and growth factors in BM cell niches from patients with CML can be demonstrated by RNA sequencing. between them,CXCL14was lost in BM cell niches, in contrast to its expression in healthy BM. Restoration of CXCL14 significantly inhibited maintenance of CML-LSC and improved its response to imatinibin vitro,and implementation of CMLlivein NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in NSG-SGM3 xenograft mice, even more so than imatinib, and this inhibition persisted in patients with a suboptimal TKI response. Mechanistically, CXCL14 increased inflammatory cytokine signaling but reduced mTOR signaling and oxidative phosphorylation in CML-LSCs. Together we discovered a silencing role for CXCL14 in CML LSC growth. CXCL14 may offer a treatment option for CML-LSCs.
(Video) Immune Thrombocytopenia (ITP) | Most COMPREHENSIVE ExplanationResearch Article
Unraveling the genetic basis of immune thrombocytopenia: current evidence for a genetic predisposition to ITP in adults
Blood advances, 2023
Immune thrombocytopenia (ITP) results from a complex, still not fully understood, deregulation of the immune system. Proposed mechanisms include autoantibody-induced platelet destruction, reduced platelet production, and abnormalities in T cell immunity, such as B. Th1 polarization, high proportion of Th17 cells, and reduced number of regulatory T cells. Although the etiology of ITP is incompletely understood and considered to be multifactorial in most cases, genetic variants are believed to play a key role in susceptibility to ITP, particularly in persistent or chronic ITP. Efforts are currently being made to discover possible predisposing genetic factors for the development of ITP. Single nucleotide polymorphisms and copy number variations have been identified in several immune-related genes such as . B. Cytokine genes, Fc gamma receptor genes, or T-cell costimulation genes identified and associated with patient susceptibility to ITP. However, due to clinical heterogeneity and the low incidence of ITP, it remains a challenge to perform genetic analyzes with a large enough sample size in informative patient populations, underscoring the need to collect well-annotated biomaterials in clinical trials or registry projects. . Another important challenge is to go beyond association studies and establish genotype-phenotype associations to demonstrate a causal relationship between a genetic alteration and the pathogenesis of ITP. This review summarizes our current understanding of the genetic alterations that have been identified as potentially predisposing factors for the development of ITP in adults, with a focus on signaling pathways considered crucial in the pathogenesis of ITP.
Research Article
Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphoma: results from 15 US institutions
Blood advances, 2023
Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed results in small cohorts of patients with aggressive B-cell lymphoma after failure of CAR-T cell therapy. To further define the efficacy of CPI therapy in this population, we retrospectively evaluated the clinical outcomes of a large cohort of 96 patients with aggressive B-cell lymphoma who were admitted after CAR-T failure at 15 US academic centers who received CPI therapy. . Most patients (53%) had DLBCL, were treated with axicabtagene-ciloleucel (53%), relapsed early (≤ 180 days) after CAR-T (83%) and received pembrolizumab (49%) or nivolumab (43%) . CPI therapy was associated with a 19% overall response rate and a 10% complete response rate. The median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes of CPI therapy significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 versus 51 days) and OS (387 versus 131 days) were significantly longer in patients with late (>180 days) versus early (>180 days) relapse ≤180 days) after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, mainly due to progressive disease. Only 5% responded consistently to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results indicate poor outcomes, particularly in those who began shortly after the CAR-T relapse had relapsed. In conclusion, CPI therapy is not an effective rescue strategy for most patients after CAR-T, as alternative approaches are needed to improve outcomes after CAR-T.
(Video) ISTH Academy Presentation: Thrombotic Thrombocytopenic Purpura (TTP)
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The authors also contributed
© 2023 of the American Society of Hematology
FAQs
What antibodies are in thrombotic thrombocytopenic purpura? ›
This form or TTP is considered to be an autoimmune disease and is caused when patients develop an antibody against the ADAMTS13 protease leading to low levels of the protease. If the disorder is present at birth (familial form), signs and symptoms may typically appear earlier, in infancy or early childhood.
How do ADAMTS13 and vwf interact? ›Proteolysis of VWF by ADAMTS13.
In its globular conformation, the A3 domain collagen binding site is exposed. ADAMTS13 can bind to this globular VWF via its TSP (5-8) and CUB domains (C), step 1. This enables VWF and ADAMTS13 complexes to form and circulate in plasma.
Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia classically characterized by the pentad of fever, hemolytic anemia, thrombocytopenia, and renal and neurologic dysfunction.
What causes TTP blood disorder? ›The cause of TTP is often unknown, but some people develop it after taking certain drugs (including quinine, cyclosporine, and mitomycin C), after certain types of intestinal infection, during pregnancy, or rarely as an inherited disease. In most people, TTP is an autoimmune disorder.
What is the mechanism of action of TTP? ›The underlying mechanism typically involves antibodies inhibiting the enzyme ADAMTS13. This results in decreased break down of large multimers of von Willebrand factor (vWF) into smaller units. Less commonly TTP is inherited, known as Upshaw–Schulman syndrome, such that ADAMTS13 dysfunction is present from birth.
What is the immune response to ITP? ›In ITP, the immune system is stimulated to attack your body's own platelets. Most often this is a result of antibody production against platelets. In a small number of cases, a type of white blood cell called T-cells will directly attack platelets.
What is the mechanism of action of ADAMTS13? ›The ADAMTS13 enzyme processes a large protein called von Willebrand factor. This protein is involved in the first step of blood clotting at the site of injury, which is to help cells called platelets stick together and attach to the walls of blood vessels, forming temporary clots.
What is the mechanism of VWF ADAMTS13? ›ADAMTS13 is secreted into plasma as a constitutively active enzyme at a plasma concentration of, approximately, 1 μg/ml [12–14]. It cleaves a large adhesive glycoprotein, von Willebrand factor (VWF), that plays an essential role in primary hemostasis by recruiting platelets to the site of vessel injury [15].
Is ADAMTS13 a VWF cleaving protease? ›The congenital or acquired deficiency of the von Willebrand factor (VWF) cleaving protease, ADAMTS-13 has been specifically associated with a diagnosis of thrombotic thrombocytopenic purpura (TTP), a microangiopathy characterized by the formation of occlusive platelet thrombi.
What enzyme is mainly affected in TTP? ›What causes TTP? TTP occurs when you do not have the right amount of an enzyme (a type of protein in your blood) called ADAMTS13. This enzyme controls how your blood clots. If you do not have enough ADAMTS13, your body makes too many blood clots.
Why does TTP cause hemolysis? ›
Pathophysiology of TTP
Loose strands of platelets and fibrin are deposited in multiple small vessels and damage passing platelets and red blood cells (RBCs), causing significant thrombocytopenia and anemia (microangiopathic hemolytic anemia).
TTP is divided into congenital (inherited) and immune-mediated (acquired) TTP. Congenital TTP (also called Upshaw–Schulman syndrome) is caused by biallelic mutations in the ADAMTS13 gene [8]. Immune-mediated TTP (iTTP) is an autoimmune disorder resulting from the production of autoantibodies against ADAMTS13 [1-3].
Why a deficiency of ADAMTS13 causes clotting because of TTP? ›A lack of activity in the ADAMTS13 enzyme (a type of protein in the blood) causes thrombotic thrombocytopenic purpura (TTP). The ADAMTS13 gene controls the enzyme, which is involved in blood clotting. Not having enough enzyme activity causes overactive blood clotting.
What causes ADAMTS13 deficiency? ›ADAMTS13 deficiency can be acquired or congenital
Secondary (23 to 67 percent of cases), arising from a variety of conditions, including autoimmune disorders, solid organ or hematopoietic cell transplant, malignancy, drugs and pregnancy.
Cardiovascular disease is a leading cause of death in patients that survive their first episode of TTP.
How does rituximab work for TTP? ›Rituximab as elective therapy to prevent TTP relapse
Rituximab is used to prevent relapse in patients with a fall in ADAMTS13 activity and symptoms based on the patient's relapse history. The target is normalisation of ADAMTS13 activity as above.
Corticosteroids. Corticosteroids are used in the acute management of acquired TTP, and should be started upfront together with PEX. Steroids are believed to suppress the production of anti-ADAMTS13 autoantibodies.
What is the primary mechanism of ITP? ›The pathophysiology of ITP is complex and abnormalities of both the B-cell and the T-cell compartments have been identified. The mechanisms of the thrombocytopenia involve both increased platelet destruction and, in a significant proportion of cases, impaired platelet production.
How does immunoglobulin work in ITP? ›In patients with ITP, Intravenous immunoglobulin (IVIG) increases the platelet count by decreasing the destruction of platelets in your spleen. IVIG may also work in patients with or without a spleen by binding to and neutralizing the antibodies responsible for destroying platelets.
What antibodies destroy platelets? ›With ITP, your immune system attacks your body's own platelets by mistake. Most often, this is a result of antibody production against platelets. In a small number of cases, a type of white blood cell called T-cells will directly attack platelets.
Which immunoglobulin is responsible for ITP? ›
In immune thrombocytopenia (ITP), an abnormal autoantibody, usually immunoglobulin G (IgG) with specificity for one or more platelet membrane glycoproteins, binds to circulating platelet membranes.
What is an ADAMTS13 inhibitor? ›ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) is a plasma protein responsible for regulating the interaction of platelets with von Willebrand factor (VWF) and physiologic proteolytic cleavage of ultra large (UL) VWF multimers at the Tyr(1605)- Met(1606) bond in the A2 domain ...
What is the ADAMTS13 level in TTP? ›An ADAMTS13 activity level of less than 10% supports the diagnosis of TTP in appropriate clinical contexts, but many centers do not offer testing in-house and must send out the test to a reference laboratory with a turnaround time of several days.
What is the mechanism of action of rituximab in ITP? ›The mechanism of action of rituximab in ITP is assumed to be due to selective depletion of CD20+ B cells, which affects autoantibody development.
What is the role of ADAMTS13 in hemostasis? ›ADAMTS13 cleaves the polymeric force-sensor von Willebrand factor (VWF) that unfolds under shear stress and recruits platelets to sites of vascular injury. Shear force–dependent cleavage at a single Tyr–Met peptide bond in the unfolded VWF A2 domain serves to reduce the size of VWF polymers in circulation.
What is the role of VWF and fibrinogen in platelet function? ›It has been demonstrated that von Willebrand factor (VWF) and fibrinogen (Fg) are two essential molecules that mediate platelet adhesion and aggregation [1]. Deficiencies in either of these molecules are associated with bleeding disorders [i.e. von Willebrand disease (VWD) and afibrinogenemia].
What is the difference between TTP and ITP? ›ITP is an autiommune disorder in which the body destroys its own platelets. TTP can occur if you do not have the right amount of an enzyme that controls how your blood clots.
Does VWF bind directly to platelets? ›VWF binds to collagen and then tethers platelets to the collagen surface through interaction with platelet glycoprotein Ib and also contributes to the thrombus formation on the collagen surface.
What receptor does VWF bind on platelets? ›The adhesion molecule von Willebrand factor (vWF) activates platelets upon binding 2 surface receptors, glycoprotein (GP) Ib-V-IX and integrin IIbβ3.
What does von Willebrand factor bind to? ›VWF has a central role in primary haemostasis where it mediates platelet adhesion to damaged vascular subendothelium and subsequently platelet aggregation. Following a vascular injury, VWF binds specifically to fibrillar collagen type I and III.
Why is fibrinogen normal in TTP? ›
D-dimer and fibrinogen assay findings are as follows: D-dimers are indicative of fibrinolysis and thus, thrombin activation, which usually is normal or mildly elevated in patients with TTP. Fibrinogen typically is in the high to high-normal range.
Is ADAMTS13 low in TTP? ›Prognostic Value of ADAMTS13 Testing in TTP
Patients with inherited TTP usually have very low plasma levels of ADAMTS13, both during acute disease and during disease-free periods.
Elevated serum lactate dehydrogenase (LDH) is a characteristic finding in patients with thrombotic thrombocytopenic purpura (TTP). It is widely accepted that total serum LDH principally rises due to the release of red blood cell LDH as a consequence of intravascular hemolysis.
What is the pathogenesis of thrombocytopenic purpura? ›The pathogenesis of ITP remains unclear although both antibody-mediated and/or T cell-mediated platelet destruction are key processes. In addition, impairment of T cells, cytokine imbalances, and the contribution of the bone marrow niche have now been recognized to be important.
Can you have TTP without hemolysis? ›In these cases, the absence of thrombocytopenia and hemolytic anemia can be explained by an early stage of TTP when platelet aggregation and thrombosis are not yet diffuse. Indeed, schistocytes are initially absent in up to 30% of patients, and blood smear examination should be regularly repeated.
What are immune mediated causes of thrombocytopenia? ›Immune thrombocytopenia usually happens when your immune system mistakenly attacks and destroys platelets, which are cell fragments that help blood clot. In adults, this may be triggered by infection with HIV , hepatitis or H. pylori — the type of bacteria that causes stomach ulcers.
What protein is used to diagnose TTP? ›By drawing a small amount of blood from your arm, the OSUCCC – James experts can analyze the sample to determine if the ADAMTS13 enzyme (a protein in the blood) is active. Most cases of TTP are caused by a problem with this enzyme.
What happens in ADAMTS13 deficiency? ›In humans, genetic or acquired deficiency in ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi.
What is inherited TTP usually a deficiency of? ›TTP is specifically related to a severe deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), the specific von Willebrand factor-cleaving protease.
Which disease is associated with an increased risk for developing TTP? ›Other risk factors that can trigger TTP include: Diseases and conditions such as cancer, HIV, lupus, infections and pregnancy. Some medical procedures such as surgery and blood- and marrow-stem cell transplant.
What is the most common antibody found in post transfusion purpura? ›
Post-transfusion purpura (PTP) is a rare yet serious disease characterized by severe thrombocytopenia occurring after a blood transfusion. It is caused by alloimmunization against platelet antigens, anti-HPA-1a being the most frequent antibody.
What is the gold standard test for TTP? ›Coombs Test
This test can tell whether TTP is causing anemia by determining if certain proteins are destroying red blood cells. If the test is negative, TTP is the cause.
Antiphospholipid syndrome (APS) is an autoimmune disorder that is associated with pregnancy complications, including preeclampsia, thrombosis, autoimmune thrombocytopenia, fetal growth restriction, and fetal loss.
Which test is diagnostic for thrombotic thrombocytopenic purpura? ›Diagnostic tests used to confirm thrombotic thrombocytopenic purpura may include: Complete blood count (CBC). A CBC measures the number of platelets as well as the number of red blood cells and white blood cells. People with TTP have a lower number of red blood cells and platelets.
How is immune thrombocytopenic purpura treated with IVIG? ›Intravenous immune globulin (IVIG) is a treatment for immune thrombocytopenia (ITP). IVIG is given by IV infusion over several hours. IVIG works to slow down the destruction of platelets. Your child will get medicine such as Tylenol® or Benadryl® to help with side effects.
What is the mechanism of post transfusion purpura? ›Post-transfusion purpura is a rare transfusion-related complication that often goes undiagnosed. It is due to alloimmunization against platelet antigens which leads to acute profound thrombocytopenia following the transfusion of any platelet-containing product (red blood cells or platelets).
What is the difference between ITP and post transfusion purpura? ›The main distinctions between PTP and ITP are the sudden development of severe thrombocytopenia in the days after transfusion in the former, as well as the presence of platelet-specific antibodies in PTP and broadly reactive or no antibodies in ITP.
How do you confirm diagnosis of TTP? ›Diagnostic laboratory testing including an ADAMTS13 activity assay, ADAMTS13 functional inhibitor assay, and anti-ADAMTS13 antibody assay may be useful, both as a means of distinguishing TTP from other TMAs and as a means of differentiating iTTP from cTTP.
How can you tell the difference between DIC and TTP? ›TTP-HUS and DIC can usually be distinguished on the basis of their occurrence in different clinical settings (ie, trauma or sepsis for DIC and fever associated with thrombocytopenia and a microangiopathic hemolytic anemia for TTP-HUS).
What is included in laboratory manifestation of TTP? ›Laboratory studies for suspected TTP include a CBC, platelet count, blood smears, coagulation studies, BUN creatinine, and serum bilirubin and lactate dehydrogenase.
What autoimmune disorders are associated with thrombocytopenia? ›
Immune thrombocytopenic purpura (ITP) is a rare autoimmune disorder, in which a person's blood doesn't clot properly, because the immune system destroys the blood-clotting platelets. The cause of ITP is not known, but it is due to an immune system error that may be triggered by viral infections.
Which antithrombotic drug is most likely to cause thrombocytopenia? ›Glycoprotein IIb/IIIa receptor antagonists, a class of antithrombotic drugs, are a common cause of DIT and can induce life-threatening thrombocytopenia.
What are the 3 antiphospholipid antibodies? ›The three known APLA are: Anticardiolipin antibodies IgG or IgM (ELISA) Anti-beta-2-glycoprotein-I antibodies IgG or IgM (ELISA) Lupus anticoagulants (Functional assays)
Is thrombotic thrombocytopenic purpura the same as ITP? ›Immune thrombocytopenia (ITP) and thrombotic thrombocytopenic purpura (TTP) are two separate diseases that are characterized by low platelets.